A main challenge in cancer therapy is the selective delivery of cytotoxic agents to tumor cells. These cytotoxic agents can be small molecules or macromolecules (e.g. proteins, DNA and siRNA), and can have either extracellular or intracellular targets. Much research in cancer therapy has focused on improving the targeted delivery of small molecule drugs such as doxorubicin, which generally have poor selectivity to tumor cells.
More recently, the use of monoclonal antibodies such as Herceptin to specifically target tumor cells that overexpress the cell-surface Her2 receptor has emerged as a viable strategy to achieve targeted cancer therapy.1,2 Monoclonal antibodies that are used today generally target extracellular receptors. However, there is a wide range of intracellular proteins in cancer cells that can be targeted by antibodies with intracellular targets, otherwise known as intrabodies.3,4 An intrabody conjugated to caspase 3 which triggers apoptosis upon antibody-antigen interaction is a prime example of a potential intrabody-based cancer therapy.5 
Some common methods of delivering intrabodies are: (i) the transfection of recombinant DNA coding the intrabody into cancer cells, resulting in intracellular expression of the intrabody, and (ii) the fusion of protein transduction domains to the intrabody to make it more cell-permeable.6 The first method usually requires the use of viral vectors, which raise safety concerns for human clinical use. Furthermore, protein folding and stability of the expressed intrabody in the successfully transfected cancer cells may be affected by the reducing intracellular environment. In the second method, the intrabody protein being delivered is not protected from degradation, and is even modified to include a transduction domain, which may compromise intrabody activity and hence its intracellular function. Neither of theses existing methods enable the active targeting of tumor cells, which is important to minimize any side effects of the intrabody being delivered.